Large-dose opioid induction of anesthesia can lead to difficult ventilation via a mask. Poor ventilatory compliance (VC) may be secondary to "rigid" chest and abdominal wall musculature, glottic closure, or upper airway obstruction. This double-blind study assessed the contribution of the upper airway to poor VC by inducing sufentanil anesthesia in patients undergoing cardiac surgery who are ventilated via a mask (Group M) or endotracheal tube fiberoptically inserted (Group E). After induction of anesthesia with sufentanil 3 microgram/kg from time (T) = 0 min to T = 2 in Group M (n = 17) or Group E(n = 23), VC and adductor pollicis (AP) twitch tension was measured continuously. Immediately prior to muscle relaxant (pipecuronium or doxacurium) administration at T = 3, Group E demonstrated significantly better VC (46 mL/cm H2O [39-55 interquartile range (IQR)]) than Group M (19 mL/cm H2O [7-24 IQR]). The effect of muscle relaxant administration on VC preceded its effect at the AP. After complete relaxation of the AP at T = 9, both groups had similar VC. Difficult ventilation during sufentanil induction of anesthesia lies at the level of the glottis or above. Bypassing these structures with an endotracheal tube overcomes the usual decreased VC.